peaks between and days of life in the term infant, rarely exceeds 12 mg/dL, and requires no treatment Gilbert syndrome is a common cause of mild, intermittent, unconjugated hyperbilirubinemia that occurs in approximately 6% of the population Patients with Gilbert syndrome have a partial deficiency of glucuronyl transferase They generally present in late childhood with nonspecific abdominal pain, nausea, and mild jaundice in the setting of an intercurrent illness; there is no hepatosplenomegaly on physical examination and the remainder of liver function studies is normal The serum bilirubin rarely exceeds mg/dL in this benign cause of jaundice Crigler–Najjar syndrome is characterized by the absence or deficiency of the enzyme bilirubin glucuronyl transferase Type I is the more severe form, manifests soon after birth, and is associated with high morbidity and mortality Type II is milder, and is caused by an incomplete deficiency of the same enzyme; it typically presents in infancy or later in childhood Lucey–Driscoll syndrome is a form of transient familial hyperbilirubinemia, and is caused by an inhibitor of glucuronyl transferase in the mother’s serum; the syndrome resolves as the inhibitor is cleared from the neonate’s blood Infants with galactosemia may exhibit an unconjugated hyperbilirubinemia during the first week of life, whereas older infants with galactosemia tend to have a conjugated hyperbilirubinemia (see Chapter 44 Jaundice: Conjugated Hyperbilirubinemia ) Infants with galactosemia typically present with poor feeding, emesis, abdominal distention, failure to thrive, and hypoglycemia Unconjugated hyperbilirubinemia may be the only presenting sign of congenital hypothyroidism, preceding other manifestations by several weeks The mechanism is thought to relate to reduced bile flow Other signs include poor feeding, prolonged jaundice, constipation, and hypotonia Infants of diabetic mothers are also at increased risk for jaundice, with as many as 19% developing nonphysiologic hyperbilirubinemia Breast milk jaundice occurs in 1% of newborns, and must be distinguished from breast-feeding jaundice (discussed below); it is associated with the breast milk itself and typically manifests after the fifth day of life The underlying cause of breast milk jaundice is incompletely understood, but is likely hormonally mediated, and involves inhibition of bilirubin conjugation Treatment requires temporary cessation of breast-feeding; however, the mother should be encouraged to express and store her breast milk during this time, and may resume breastfeeding when the neonatal bilirubin level reverts to normal Impaired Bilirubin Excretion